Is DPPA3 p.Pro128Ser (c.382C>T) pathogenic?

DPPA3 p.Pro128Ser (c.382C>T) is classified Uncertain significance in DPPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1962); Very rare (popmax 0.000424%, nfe).

How common is DPPA3 p.Pro128Ser (c.382C>T) in the general population?

DPPA3 p.Pro128Ser (c.382C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DPPA3 p.Pro128Ser (c.382C>T)?

AlphaMissense predicts likely benign (score 0.1962) — an in-silico prediction, not a clinical call.

DPPA3 p.Pro128Ser

c.382C>T · VCV4244576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1962	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -2.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.3
Regional constraint	o/e 0.76	unconstrained · MANE · 5,503 bp · p 0.00084 · regional, not allelic
Overall
CADD	0.642	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,022 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,460,578 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DPPA3
Protein: p.Pro128Ser
Coding: c.382C>T
MANE Select: NM_199286
Type: single nucleotide variant
Location: chr12:7716979 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.46 · 3 PDB

Full DPPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPPA3 p.Ala147Val Uncertain significance ★ ⚠ same type
DPPA3 p.Arg108Cys Uncertain significance ★ ⚠ same type
DPPA3 p.Arg24Trp Uncertain significance ★ ⚠ same type
DPPA3 p.Arg62Gly Uncertain significance ★ ⚠ same type
DPPA3 p.Arg83Gly Uncertain significance ★ ⚠ same type
DPPA3 p.Arg98Ser Uncertain significance ★ ⚠ same type
DPPA3 p.Asn116Asp Uncertain significance ★ ⚠ same type
DPPA3 p.Asn151Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dppa3-p-pro128ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown